The aims of these experiments are to examine the possible mechanisms of the chemopreventive effects of selenium. Extensive experiments have documented the chemopreventive efficacy of selenium for a wide variety of epithelial tumors, however there is a dearth of information on the mechanisms of selenium action. Recent experiments have indicated the presence of several selenoproteins in rodent tissues. So far, there is no definitive information on the possible functions of these proteins. Our experiments have focused on a 60K dalton selenoprotein whose expression appears to be diminished in non-cycling cells. The experiments proposed herein will examine the expression of the 60K protein and several other parameters of selenium exposure in mammary preneoplasias with respect to dietary selenium levels and tumorigenic response. The possible synergistic effects of vitamin E and selenium will also be examined in the in vivo model system. The relationships between selenium concentration, 60K selenoprotein, general protein synthesis and protein phosphorylation will be examined in an in vitro model system using mouse mammary epithelial cells. The hypothesis that the chemopreventive effects of selenium on cell growth are mediated by modification of protein function will be pursued by examining protein phosphorylation and protein synthesis.

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National Cancer Institute (NCI)
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Metabolic Pathology Study Section (MEP)
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Baylor College of Medicine
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Medina, Daniel; Kittrell, Frances (2005) Stroma is not a major target in DMBA-mediated tumorigenesis of mouse mammary preneoplasia. J Cell Sci 118:123-7
Kong, Gu; Chua, Steven S; Yijun, Yi et al. (2002) Functional analysis of cyclin D2 and p27(Kip1) in cyclin D2 transgenic mouse mammary gland during development. Oncogene 21:7214-25
Medina, Daniel (2002) Biological and molecular characteristics of the premalignant mouse mammary gland. Biochim Biophys Acta 1603:1-9
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Said, T K; Moraes, R C; Sinha, R et al. (2001) Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth. Breast Cancer Res 3:122-33
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Lydon, J P; Ge, G; Kittrell, F S et al. (1999) Murine mammary gland carcinogenesis is critically dependent on progesterone receptor function. Cancer Res 59:4276-84
Said, T K; Medina, D (1998) Interaction of retinoblastoma protein and D cyclins during cell-growth inhibition by hexamethylenebisacetamide in TM2H mouse epithelial cells. Mol Carcinog 22:128-43
Said, T K; Conneely, O M; Medina, D et al. (1997) Progesterone, in addition to estrogen, induces cyclin D1 expression in the murine mammary epithelial cell, in vivo. Endocrinology 138:3933-9
Medina, D (1996) The mammary gland: a unique organ for the study of development and tumorigenesis. J Mammary Gland Biol Neoplasia 1:5-19

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